autologous CD34+ hematopoietic stem cells transduced with GLOBE lentiviral vector encoding human beta-globin

Autologous CD34+ hematopoietic stem cells transduced with GLOBE lentiviral vector encoding human beta-globin (also known as OTL-300 or GSK-2696277) is an investigational ex vivo gene therapy developed for the treatment of transfusion-dependent beta-thalassemia (TDT). The therapy consists of a patient's own CD34+ hematopoietic stem and progenitor cells (HSPCs) that are genetically modified ex vivo using the GLOBE lentiviral vector—a self-inactivating, replication-deficient lentiviral vector derived from HIV-1—to deliver a transcriptionally regulated human beta-globin gene. Following myeloablative conditioning chemotherapy, the engineered cells are reinfused (often intraosseously or intravenously) where they engraft and produce functional beta-globin protein in erythroid cells, thereby restoring hemoglobin production and reducing or eliminating the need for chronic blood transfusions. The program originated from a collaboration between Ospedale San Raffaele, Fondazione Telethon, and GSK, and was later licensed to Orchard Therapeutics (now a subsidiary of Kyowa Kirin), though Orchard subsequently returned the rights to the original academic licensors.

Other names

autologous hematopoietic stem cells genetically modified with GLOBE lentiviral vector encoding for the human beta-globin geneGLOBE lentiviral beta-globin gene therapy